全反式维甲酸联合猪胆酸钠对人卵巢癌细胞生长抑制作用的影响

目的 探讨维甲酸（ATRA）及猪胆酸钠（SBANa)联合反应对人卵巢癌细胞生长的抑制作用。方法 实验共分为三组：单用ATRA组、单用SBANa组及ATRA＋SBANa联合用药组。应用MTT比色法、流式细胞仪对COC1、COC2、CAOV3三种卵巢癌细胞系在不同浓度的ATRA及SBANa下进行检测。结果 ATRA及SBANa联合应用后，能增强抑制卵巢癌细胞生长作用，当达到ATRA10μmol/L SBANa 100μg/ml浓度时，G0、G1期细胞比例增加，G2M、S期细胞比例下降，细胞增殖速度较单独用药组减缓。MTT检测提示在联合用药浓度达到ATRA 10μmol/L SBANa 100μg/ml时，癌细胞抑制率最佳。结论 ATRA及SBANa联合应用可增强对卵巢癌细胞增殖的抑制作用，并在ATRA 30μmol/L SBANa 100μg/ml浓度时，促进癌细胞凋亡。     

蜂胶抗肿瘤活性成分的研究

采用溶媒萃取法和硅胶柱层析法从蜂胶中获得了两种具有抗肿瘤活性的组分PPLCC和PPLSE,体外抗肿瘤细胞人肝癌细胞(HepG2)和人口腔癌细胞(KB)试验表明,浓度为50μg/ml的PPLCC和PPLSE对HepG2细胞的抑制率分别达87.4%和35.1%,IC50分别为17.5μg/ml和1151.2μg/ml;对KB细胞的抑制率分别为84.9%和59.8%,IC50分别为21.0μg/ml和33.6μg/ml。结果表明,蜂胶可作为抗肿瘤活性物质的天然来源。     

抗肿瘤抗生素CC-1065(NSC298223)和DNA相互作用的机制研究

抗肿瘤抗生素 CC-1065是由链霉菌产生的三环化合物,小鼠 LD50为25μg/kg,对小鼠白血病 L_(1210)、P338、黑色素瘤 B_(16)和结肠癌有明显抑制作用,对体外培养的人肿瘤细胞也有作用,对 L_(1210)细胞的抑制作用,其浓度为0.02和0.05μg/ml,抑制率分别为50、     

噻替派(Thiotepa)滴眼液对人癌细胞和正常细胞的细胞毒作用

目的 了解0.05%Thiotepa滴眼液对各种不同的人癌细胞和正常细胞生长的影响.方法 采用四甲基偶氮唑蓝(MTT)法进行体外细胞毒试验,测定Thiotepa滴眼液对人癌细胞和正常细胞的生长抑制作用,以半数抑制浓度(IC50值)进行评价.结果 Thiotepa滴眼液在50μg/ml～0.78μg/ml浓度下对人癌细胞Glc-82、K-562、Bel-7402、Hela和CNE2的IC50值依次为:22.7μg/ml、10.6μg/ml、15.3μg/ml、11.2μg/ml和9.6μg/ml.对人正常细胞Hk-293、ECV-304、HRPE、Fibro和小鼠3T3细胞的IC50值分别为:1.4μg/ml、12.5μg/ml、17.8μg/ml、36.6μg/ml和14.4μg/ml.结论 Thiotepa滴眼液对各种细胞有明显的生长抑制作用;0.05%Thiotepa滴眼液对各种人癌细胞和正常细胞均有强的细胞毒作用,且对人癌细胞无明显的选择性抑制作用.     

血卟啉衍生物—光辐射对L1210白血病细胞核酸生物合成的影响

本文报道几种血卟啉衍生物—光辐射效应对L1210白血病细胞DNA及RNA生物合成有不同程度的抑制。对DNA生物合成抑制的IC_(50),HA 308为2.1μg/ml,激光3号为2.5μg/ml,LF-019为3.6μg/ml,Photofrin Ⅱ>5μg/ml,对RNA生物合成抑制的IC_(?) LF-019为3.7μg/ml,激光3号为5.7 μg/ml,HA 308为8.8 μg/ml,photofrin Ⅱ>10 μg/ml.其中激光3号对DNA聚合酶α的光动力学失活作用也较明显。     

黄曲霉毒素B_1对肝癌细胞株SMMC-7721的作用研究

目的通过用黄曲霉毒素B1（AFB1）处理人肝癌细胞株SMMC-7721研究AFB1对SMMC-7721细胞生长的影响。方法①首先应用96孔板培养细胞,选择适宜的细胞接种密度进行实验。②应用不同浓度的黄曲霉毒素B120g/ml、10g/ml、5g/ml、2g/ml、1.0g/ml、0.1g/ml、0.01g/ml处理人肝癌细胞株SMMC-7721,MTT法绘制细胞生长曲线,观察黄曲霉毒素B1对肝癌细胞株SMMC-7721生长的影响。结果不同浓度的AFB1对肝癌细胞株SMMC-7721的影响不同,AFB120.0g/ml、AFB110.0g/ml、AFB15.0g/ml表现为细胞毒性,呈浓度依赖性;AFB11.0g/ml、AFB10.1g/ml、AFB10.01g/ml对肝癌细胞株SMMC-7721的增殖活性具有促进作用,以AFB11.0ug/ml浓度显著,AFB10.1 g/ml、AFB10.01g/ml作用渐减弱。结论黄曲霉毒素B11.0g/ml具有增强人肝癌细胞株SMMC-7721增殖活性的作用。     

从小球藻、栅藻和类似绿藻纲植物中提得抗肿瘤成分

所得成分为分子量120 000和70 000的糖蛋白,前者对小鼠L_(1210)的半数抑制浓度IC_(50)为5μg/ml,后者的IC_(50)为17μg/ml。     

LncRNA ITGB2-AS1靶向miR-338-3p对肺癌细胞多西他赛耐药性的影响

目的 研究lncRNA ITGB2-AS1对肺癌细胞增殖、凋亡及多西他赛耐药性的影响及潜在的分子机制.方法 用不同浓度(6.25μg/L、12.5μg/L、25μg/L、50μg/L、100μg/L、200μg/L)多西他赛(DTX)处理肺癌A549和多西他赛耐药细胞A549/DTX细胞,CCK8法测定DTX对A549...     

248株念珠菌和新型隐球菌对四种抗真菌药的敏感性

目的　检测 2 48株念珠菌和新型隐球菌对四种抗真菌药氯康唑、两性霉素B、5 氟胞嘧啶和酮康唑的耐药状况。方法　收集临床菌株新型隐球菌 6 0株和念珠菌 188株 ,采用NCCLSM2 7 A微量稀释法测定新型隐球菌和念珠菌临床分离株对四种抗真菌药物的最低抑菌浓度 (MIC)。结果　对 16 0株白念珠菌 ,氟康唑的MIC为 0 .0 6～≥ 6 4μg/ml,敏感 135株 ( 84.38% ) ,中度敏感 10株 ( 6 .2 5 % ) ,耐药 15株 ( 9.37% ) ;5 氟胞嘧啶的MIC为 0 .0 6～ 16 μg/ml ,敏感 15 6株 ( 97.5 % ) ,中度敏感 2株 ( 1.2 5 % ) ,耐药 2株 ( 1.2 5 % ) ;两性霉素B的MIC为 0 .0 6～ 4μg/ml全部敏感 ;酮康唑的MIC为 0 .0 3～ 32 μg/ml ,敏感 93.75 % ,中度敏感 6 .2 5 %。对 6 0株新型隐球菌 ,氟康唑的MIC 1～≥ 6 4μg/ml,敏感 35株 ( 5 8.4% ) ,中度敏感 2 0株 ( 33.3% ) ,耐药 5株( 8.3% ) ;5 氟胞嘧啶MIC 0 .2 5～ 8μg/ml,敏感 5 3株 ( 88.3% ) ,中度敏感 7株 ( 11.7% ) ;两性霉素B的MIC为 0 .0 6～ 0 .5 μg/ml全部敏感 ;酮康唑MIC 0 .0 3～ 4μg/ml全部敏感。热带念珠菌和光滑念珠菌对氟康唑耐药率分别为 10 %和2 2 .2 %。结论　新型隐球菌和念珠菌对氯康唑的耐药率趋高 ,临床不容忽视。     

血卟啉衍生物—光辐射对L1210白血病细胞核酸生物合成的影响

本文报道几种血卟啉衍生物—光辐射效应对L1210白血病细胞DNA及RNA生物合成有不同程度的抑制。对DNA生物合成抑制的IC₅₀,HA 308为2.1μg/ml,激光3号为2.5μg/ml,LF-019为3.6μg/ml,Photofrin Ⅱ>5μg/ml,对RNA生物合成抑制的IC₅₀ LF-019为3.7μg/ml,激光3号为5.7 μg/ml,HA 308为8.8 μg/ml,photofrin Ⅱ>10 μg/ml.其中激光3号对DNA聚合酶α的光动力学失活作用也较明显。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.